Tuesday, August 31, 2010

Cushing's Syndrome (CS) which is caused by isolated Corticotropin-releasing hormone (CRH) production, rather than adrenocorticotropin (ACTH) production, is extremely rare.

Methods: We describe the clinical presentation, course, laboratory values and pathologic findings of a patient with isolated ectopic CRH causing CS. We review the literature of the types of tumors associated with this unusual syndrome and the behavior of these tumors by endocrine testing.

Results: A 56 year old woman presented with clinical and laboratory features consistent with ACTH-dependent CS.

Pituitary imaging was normal and cortisol did not suppress with a high dose dexamethasone test, consistent with a diagnosis of ectopic ACTH. CT imaging did not reveal any discrete lung lesions but there was mediastinal and abdominal lymphadenopathy and multiple liver lesions suspicious for metastatic disease.

Laboratory testing was positive for elevated serum carcinoembryonic antigen and the neuroendocrine marker chromogranin A. Serum markers of carcinoid, medullary thyroid carcinoma, and pheochromocytoma were in the normal range.

Because the primary tumor could not be identified by imaging, biopsy of the presumed metastatic liver lesions was performed. Immunohistochemistry was consistent with a neuroendocrine tumor, specifically small cell carcinoma.

Immunostaining for ACTH was negative but was strongly positive for CRH and laboratory testing revealed a plasma CRH of 10 pg/ml (normal 0 to 10 pg/ml) which should have been suppressed in the presence of high cortisol.

Conclusions: This case illustrates the importance of considering the ectopic production of CRH in the differential diagnosis for presentations of ACTH-dependent Cushing's Syndrome.

High Prevalence of Normal Tests Assessing Hypercortisolism in Subjects with Mild and Episodic Cushing's Syndrome Suggests that the Paradigm for Diagnosis and Exclusion of Cushing's Syndrome Requires Multiple Testing

Many Endocrinologists believe that a single determination of eucortisolism or a single demonstration of appropriate suppression to dexamethasone excluded Cushing's syndrome, except in what was previously thought to be the rare patient with episodic or periodic Cushing's syndrome. We hypothesize that episodic Cushing's syndrome is relatively common and a single test assessing hypercortisolism may not be sufficient to accurately rule out or diagnose Cushing's syndrome and retrospectively examined the number of normal and abnormal tests assessing hypercortisolism performed on multiple occasions in 66 patients found to have mild and/or episodic Cushing's syndrome compared to a similar group of 54 patients evaluated for, but determined not to have Cushing's syndrome. We found that 65 of the 66 patients with Cushing's syndrome had at least one normal test of cortisol status and most patients had several normal tests. The probability of having Cushing's syndrome when one test was negative was 92% for 23:00 h salivary cortisol, 88% for 24-h UFC, 86% for 24-h 17OHS, and 54% for nighttime plasma cortisol. These results demonstrated that episodic hypercortisolism is highly prevalent in subjects with mild Cushing's syndrome and no single test was effective in conclusively diagnosing or excluding the condition. Rather, the paradigm for the diagnosis should be a careful history and physical examination and in those patients in whom mild Cushing's syndrome/disease is strongly suspected, multiple tests assessing hypercortisolism should be performed on subsequent occasions, especially when the patient is experiencing signs and symptoms of short-term hypercortisolism.

Context: Several studies have reported an association between idiopathic intracranial hypertension (IIH) and deficits of the hypothalamic-pituitary-adrenal (HPA) axis.

Case Illustration: A 33-yr-old woman with Cushing's disease underwent successful surgical resection of a pituitary adenoma and developed IIH 11 months later after inadvertent withdrawal of oral glucocorticoids.

Methods: A review of the literature was conducted to identify previous studies pertaining to IIH in association with neuroendocrine disease, focusing on reports related to HPA axis dysfunction.

Results: A number of patients developing IIH due to a relative deficiency in glucocorticoids, after surgical or medical management for Cushing's disease, withdrawal from glucocorticoid replacement, or as an initial presentation of Addison's disease, have been reported. Hypotheses regarding the underlying pathophysiology of IIH in this context and, in particular, the role of cortisol and its relationship to other neuroendocrine and inflammatory mediators that may regulate the homeostasis of cerebrospinal fluid production and absorption are reviewed.

Conclusion: In a subset of patients, dysfunction of the HPA axis appears to play a role in the development of IIH. Hormonal control of cerebrospinal fluid production and absorption may be regulated by inflammatory mediators and the enzyme 11ß-hydroxysteroid dehydrogenase type 1. Further study of neuroendocrine markers in the serum and cerebrospinal fluid may be an avenue for further research in IIH.

Wednesday, August 25, 2010

I've long suspected that my kidney cancer was connected to my growth hormone usage but I couldn't ever get doctors to confirm this. I'm sure that they were afraid of a lawsuit - or maybe GH usage is just too new, that they really don't know the side effects yet.

Thanks to Ellen for sharing this excerpt. Maybe I was right all along...

Endocrinologist Dr. Mary Lee Vance, interviewed in a story about human growth hormone damage in the New York Times T Style magazine Sunday, August 22, 2010

"There is little doubt that H.G.H. was the fertilizer for my face’s errant growths, which constituted a “true adverse effect,” in the words of Dr. Mary Lee Vance, a professor of medicine and neurosurgery at the University of Virginia Health System in Charlottesville who specializes in pituitary disorders in adults. She confirmed that growth hormone used for anti-aging purposes can lead to an overload of the hormone in the body, thus stimulating skin changes, including the development of skin tags, moles, a coarsening of the skin’s texture, enlarged pores and excess sebum production in the oil glands, along with sweat."

“There is no doubt that growth hormone stimulates the entire body, and too much can be very harmful,” she said. “If you have an undiagnosed cancer, there is the possibility of promoting growth of the tumor. In the world of endocrinology, we give hormones to replace what’s appropriate for a person’s age, not to give them the same levels as when they were 30. People taking growth hormone for anti-aging are playing with fire.”

Monday, August 23, 2010

I had my annual visit to my kidney cancer surgeon. He said that things are looking good and reminded me that chances of a recurrence are getting smaller each year as are probabilities of a metastasis. Whew! However. He asked me about the CT scans I'd had last year. I had lung nodules at that time as well as an enlarged mediastinal lymph node.

I was supposed to get those scanned fairly regularly and my PCP was supposed to order the scans. I did a couple of those then we (PCP and I) thought that maybe the radiation risk was worse than the possible findings since there was no change. So he stopped ordering the scans and I forgot all about it. Until today.

So my kidney cancer surgeon said that my PCP would no longer be in charge of these scans. He referred me to a pulmonologist. The KCS thinks there will probably be a biopsy. Yuck.

I called the hospital at 11:00am and said that I needed a CD of my scans and they said they'd be ready when I got there. I got to the hospital at 11:20 and their machine had broken. So, I waited while they made a manual copy.

I got home about noon and, of course, the pulmonologist's staff was out to lunch. I left a message for them to ca back but of course they didn't. When I called them back I got an appointment for September 8. I hope that this doesn't signal the beginning of a new medical journey.

Like Scarlet O'Hara I'll think about this...tomorrow.

I finally did it! I've been looking at Macs for a while now. I'm so tired of the Windows constant security updates. On tuesday night there were 35. Egads! I've had 5 different Macs in my amazon.com shopping card trying to decide what to get for a long time. Today I made the decision.

We leave on Saturday for our annual trip to Barbados and I'll be carrying my laptop in my backpack. Since I just had a bit of surgery on my mid-back, I want to keep things as light as possible. My Gateway weighs 7.5 pounds and the battery lasts maybe 3 hours. The Mac weighs 4.5 pounds with a 10-hour battery.

On some kind of whim, I looked at amazon.com again and they said that I could get next day shipping if I ordered by 7:30 pm. I assumed that the shipping costs would be prohibitive but I looked anyway – only $3.99. So, I ordered it and hoped that they were right about next day delivery. I hated the thought of this Macbook sitting on my front porch for 2 weeks if I missed the delivery.

Abstract: Pituitary adenomas are benign tumors that can be either secreting (acromegaly, Cushing's disease, prolactinomas) or non-secreting. Transsphenoidal neurosurgery is the gold standard treatment; however, it is not always effective. Gamma Knife radiosurgery is a specific modality of stereotactic radiosurgery, a precise radiation technique. Several studies reported the efficacy and low risk of adverse effects induced by this technique: in secreting pituitary adenomas, hypersecretion is controlled in about 50% of cases and tumor volume is stabilized or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or first-line treatment. As hormone levels decrease progressively, the main drawback is the longer time to remission (12-60 months), requiring an additional treatment during this period. Hypopituitarism is the main side effect, observed in 20-40% cases. Gamma Knife is thus useful in the therapeutic algorithms of pituitary adenomas in well-defined indications, mainly low secreting small lesions well identified on magnetic resonance imaging (MRI).

Introduction

Pituitary adenomas are usually benign tumors that can be either secreting (growth hormone in acromegaly, adrenocorticotropin hormone in Cushing’s disease, prolactin in prolactinomas) (Biller et al., 2008; Chanson et al., 2009b; Klibanski, 2010) or non-secreting (in this latter case, adenomas are frequently responsible for local compression after several years of progressive volume increase) (Dekkers et al., 2008). Despite major advances in the treatment of pituitary adenomas, definite cure remains challenging. Transsphenoidal surgery, considered as the first line treatment, induces remission in 50-80% of cases, depending on the adenoma volume, its extension to peripheral structures, the neurosurgeon’s experience, and so on. Adjunctive treatments are thus necessary, but their efficacy and tolerance are less than satisfactory. For instance, somatostatin analogs generally lead to a 50-60% remission rate in acromegaly, but relapse is the rule after withdrawal (Chanson et al., 2009a); dopamine agonists lead to a 80-90% remission rate in prolactinomas, but are sometimes poorly tolerated (Casanueva et al., 2006). Fractionated radiotherapy, another possible adjunctive treatment, though highly effective, induces a high risk of hypopituitarism (Brada and Jankowska, 2008).

Stereotactic radiosurgery has been used for years in the treatment of secreting and non-secreting pituitary adenomas, either as a primary non-surgical or as an adjunctive post-surgical treatment (Castinetti et al., 2010). Stereotactic radiosurgery is characterized by a highly precise definition of the target. It can be delivered as a single fraction using a multi-headed cobalt unit (Gamma Knife) or a linear accelerator (LINAC), or as a fractionated procedure using linear accelerator (stereotactic conformal radiotherapy). Recent studies also reported the possibility of Cyberknife multi-session radiosurgery, but data on the efficacy and adverse effects of this technique in pituitary adenomas are preliminary (Castinetti et al., 2010). The majority of the studies published to date were based on Gamma Knife: we thus decided to focus only on this approach. Reports based on other stereotactic procedures, though infrequent, reported similar levels of efficacy and risks of adverse effects compared to Gamma Knife. This latter point should allow extending the conclusions of this review to the overall role of stereotactic radiosurgery in the management of pituitary adenomas.

What Is Gamma Knife Radiosurgery?

Gamma knife stereotactic radiosurgery is a radiation therapy technique using a source of 60Cobalt where narrow ionizing beams, given in a single high-dose fraction, are used either to destroy a predetermined target volume or to induce a desired biological effect in the target volume (in other words normalize or decrease the secretion of an over-secreted pituitary hormone) (Castinetti et al., 2010). The procedure is performed without opening the skull and with minimal damage to the surrounding brain. Sparing the critical structures around the target relies on the high conformity and anatomical selectivity of the dose delivery. In contrast with stereotactic radiosurgery, conventional radiotherapy covers the lesion and the surrounding structures with a fractionated dose; its aim is to minimize the injury of the surrounding structures included in the field of irradiation by the fractionation, creating a gradient of toxicity between target cells and normal tissue. The mechanism of both techniques is thus different, leading to complementary indications that will be detailed later in this review. To obtain optimal efficacy, Gamma Knife should thus be reserved to small well-defined lesions.

The efficacy of the technique is highly correlated to the definition of the target, and according to some studies, to the target volume (Jagannathan et al., 2007; Pouratian et al., 2006) — as previously mentioned, Gamma Knife radiosurgery should be reserved to small well-defined lesions. Most of the studies did not report that target volume was a predictive factor of remission due to a bias of selection of patients (in the way that most of the patients treated by Gamma Knife present a small tumor volume). The less precise the target is, the higher the risk of adverse effects is, mainly hypopituitarism. Other positive predictive factors have been reported, including initial hormone levels and radiation dose (Castinetti et al., 2009; Jezkova et al., 2006; Pollock et al., 2008a) — but results are contradictory and do not allow to draw any firm conclusion. Previous studies also reported a so-called radioprotective effect of anti-secretory drugs given at the time of radiosurgery: for instance, patients treated by somatostatin agonists at the time of Gamma Knife were presumed to be less likely to achieve remission compared to patients without the treatment (Jagannathan et al., 2008; Jagannathan et al., 2007; Landolt et al., 2000; Landolt and Lomax, 2000; Pollock et al., 2007; Pouratian et al., 2006). The pathophysiological mechanism is unclear and results are also contradictory. As a consequence, to our knowledge, the best criterion to evaluate whether radiosurgery is the appropriate treatment is the level of definition of the target on MRI.

The main drawback of Gamma Knife is the delay to remission, and this has to be taken into account at the time of disease management decision. Due to the slow decrease of hormone levels, mean time to remission after radiosurgery is usually about 30-50 months in patients with acromegaly, and 15-30 months in patients with Cushing’s disease and prolactinomas (Castinetti et al., 2010). This delay to remission implies that Gamma Knife should either be used in patients with low secreting tumors, or in patients for whom an anti-secretory drug is at least partially effective. In this latter case, the drug should be given immediately after the procedure; regular withdrawal will allow to determine hormone levels without any anti-secretory drug, and to determine the need for maintaining the treatment (and also the efficacy of the radiosurgical procedure). In our studies, we observed that the time to remission was frequently correlated to the initial hormone levels without anti-secretory drugs (Castinetti et al., 2007; Castinetti et al., 2009; Castinetti et al., 2005). We thus think that a pre-radiosurgical evaluation of the level of hypersecretion should be performed without medical treatment. In our opinion, Gamma Knife should be reserved to tumors with a relatively low level of hypersecretion. Interestingly, the anti-tumoral effect is observed shortly after radiosurgery: in the majority of the studies, volume stabilization was reported during the first year after the procedure (Jagannathan et al., 2008; Jagannathan et al., 2007; Jezkova et al., 2006; Pamir et al., 2007; Pouratian et al., 2006). Of note, this does not justify the use of Gamma Knife radiosurgery in rapidly expanding lesions close to the optic chiasm; these lesions should still highly benefit from surgery if operable, or anti-secretory drugs as a first line treatment.

There is no major contra-indication to Gamma Knife radiosurgery. The focalized high dose delivered by radiosurgery was initially thought to be dangerous for the optical pathways; this involved the need for a minimal distance between the target volume and the chiasm and a dose to the chiasm not superior to 8 Gy. This risk seems low presently, taking into account new target definition methods and improvements in the accuracy of the radiosurgical procedure (Castinetti et al., 2010).

How to Follow Up the Patients Treated by Gamma Knife Radiosurgery?

As mentioned previously, radiosurgery has a delayed maximal efficacy, requiring effective anti-secretory treatments during this latency period. MRI evaluation should be performed 3 months after the procedure, and then yearly. Some rare cases of immediate or delayed increase of the tumor volume have been reported, which justifies the need for a prolonged follow-up (Castinetti et al., 2010; Jagannathan et al., 2008; Jagannathan et al., 2007; Jezkova et al., 2006; Pouratian et al., 2006). Usually, hormone levels tend to decrease progressively to a stable level: withdrawal of anti-secretory drugs has to be performed regularly to assess the efficacy of the procedure, and, as a consequence, to determine the appropriate time for discontinuation of the drug. Interestingly, recent long-term follow-up studies reported a risk of late recurrence in patients treated for Cushing’s disease (Castinetti et al., 2009; Jagannathan et al., 2007). In our long-term study based on 76 patients, 2 out of 10 patients considered in remission of Cushing’s disease presented recurrence 6 and 8 years after Gamma Knife (Castinetti et al., 2009). This point emphasizes the need for a prolonged follow-up, particularly in patients with Cushing’s disease, even after long-term remission.

Radiation induced hypopituitarism is the most frequent side effect. It is usually reported in 10-30% of cases, depending on the dose to the target and the stalk, the visualization of the target, previous surgical or radiotherapy procedures, etc. (Castinetti et al., 2009; Jezkova et al., 2006; Minniti and Brada, 2007; Pollock et al., 2008b; Ronchi et al., 2009; Sheehan et al., 2005). These adverse effects have been reported as early as within a year after Gamma Knife, or much later, up to ten years after the procedure (Castinetti et al., 2009; Ronchi et al., 2009). Systematic pituitary hormone evaluations should thus be performed yearly in all patients. There is also a theoretical risk of optic neuritis, evaluated to be about 2% of cases in former published series. This risk currently seems to be lower due to more precise definition techniques, and improvement of the stereotactic procedure (Ove et al., 2000; Stafford et al., 2003; Tishler et al., 1993). Other side effects, described with long-term follow-up studies of fractionated radiotherapy for brain tumors, memory loss, and cerebro-vascular accidents, seem to be rare with Gamma Knife: it could either be because the technique is more precise and harmless for the surrounding tissues, or because the length of follow-up is too short to date to detect such adverse effects.

Why to Use Gamma Knife Radiosurgery Rather Than Fractionated Radiotherapy?

Efficacy of conventional radiotherapy in controlling hormone hypersecretion is estimated to be about 50-90% of cases, regardless of the type of secretion (Brada and Jankowska, 2008). Interestingly, to our knowledge, no recurrence has ever been reported after radiotherapy. Efficacy of radiosurgery is seemingly lower, particularly for Cushing’s disease, where a 50% rate of remission was reported, which might be further decreased by potential late recurrences (Castinetti et al., 2009; Jagannathan et al., 2008). In terms of anti-tumoral efficacy, results of conventional radiotherapy are comparable to those of Gamma Knife, with unchanged or decreased tumor volume in the majority of cases. However, conventional radiotherapy has two main drawbacks: the first one is the time to remission, equal to 5-10 years which is longer than that of Gamma Knife, requiring an effective medical treatment during this period. The second drawback of radiotherapy is the risk of side effects, including hypopituitarism (in more than 80% of cases), optic neuritis, radiation induced cerebral tumors, cerebral infraction, cognitive dysfunctions, etc. (Brada and Jankowska, 2008). These latter side effects occurred after a mean time of 10-20 years, and were not (at least not yet) described with the use of Gamma knife (Ayuk and Stewart, 2009; Borson-Chazot and Brue, 2006; Jenkins et al., 2006; Kong et al., 2007; Langsenlehner et al., 2007; Minniti et al., 2009; Snead et al., 2008).

Fractionated radiotherapy and stereotactic radiosurgery should be considered as two different modalities to treat different types of tumors. We think that stereotactic radiosurgery should be reserved to small and well defined tumors, in contrast with conventional, fractionated radiotherapy for larger and/or imprecisely defined tumors. To minimize the risk of adverse effects, a discussion between the endocrinologist, the neurosurgeon, the radiotherapist, and the radiosurgery specialist is necessary to choose the most appropriate radiation therapy.

Conclusion

Gamma Knife radiosurgery (and more generally stereotactic radiosurgery) is an effective and safe technique for treating pituitary adenomas. It has a reasonable good anti-secretory and a high anti-tumoral efficacy, making it a valuable treatment in case of contra-indication or partial efficacy of transsphenoidal surgery. Due to its mechanism of action being based on a precise single high dose fraction, stereotactic radiosurgery should be reserved to small lesions well defined on imaging techniques. A regular follow-up is required after the procedure, and should take into account the risk of late recurrence, particularly in Cushing’s disease.

Compared to fractionated radiotherapy, the main advantages of stereotactic radiosurgery are the relative rapidity of the effects (with a shorter time to remission) and a theoretically lower risk of adverse effects (this latter point will have to be proven by studies with a more prolonged follow-up, identical to the ones reporting fractionated radiotherapy studies). However, as indications of both techniques are different, stereotactic radiosurgery and fractionated radiotherapy should not be considered as mutually exclusive, but more as complementary ways to treat different kinds of pituitary adenomas.

Acknowledgments

The authors would like to thank Prof. J. Regis and Prof. H. Dufour, Department of Functional neurosurgery and Department of Neurosurgery, La Timone Hospital, Marseille, France, for their support.

At present no single test is considered of absolute value in identifying patients successfully operated for Cushing's disease who are at risk for recurrence. The present report describes the first two patients in whom ACTH/cortisol abnormal responses to desmopressin disappeared after cure and then clearly reappeared during long-term follow-up several months before the clinical and hormonal features of hypercortisolism became manifest.

The case histories of 2 young women are reported. The diagnosis of Cushing's disease was made on the basis of clinical features and standard hormonal criteria. Both patients, showing abnormal ACTH/cortisol rises after desmopressin test, underwent pituitary adenomectomy by transsphenoidal surgery and after operation plasma ACTH and serum cortisol levels were 0.2 and 0.4 pmol/l and 56 and 32 nmol/l, respectively. During the follow-up both patients underwent desmopressin (10 U g iv), ovine CRH (1 U g/kg iv) and 1 mg dexamethasone tests at 1, 6, 12, 24 months after surgery.

In these two cases the ACTH/cortisol response to desmopressin normalized following pituitary adenomectomy, concomitantly with the normalization of all the other clinical and hormonal parameters. Subsequently abnormal rises after the synthetic AVP analogue administration appeared: paradoxical ACTH/cortisol increments after desmopressin occurred 24 and 6 months before any other hormonal or clinical sign of recurrence of hypercortisolism.

As desmopressin may be able to stimulate ACTH/cortisol release in Cushing's disease, but not in normal subjects, we suggest that it can have a role in early identifying successfully operated Cushing's patients at risk for recurrence.

Background: Cabergoline is a long-acting dopamine receptor agonist used to treat prolactinomas. Identification of D2-receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson’s syndrome, ectopic ACTH-secreting tumors and recently Cushing’s disease (CD).

Objective: Evaluate the long-term efficacy of cabergoline monotherapy in patients with CD.

Methods: Retrospective analysis of non-randomized clinical therapy with cabergoline in 30 patients with CD treated in academic centers of Buenos Aires and Montreal. Cabergoline was initiated at 0.5-1.0 mg/wk and adjusted up to a maximal dose of 6 mg/wk based on urinary free cortisol (UFC) levels. Complete response to cabergoline was defined as a sustained normalization of UFC with at least two normal values measured at 1 to 3 months interval; partial response was defined as a decrease of UFC to <125% of the upper limit of normal, and treatment failure as UFC ?125% of it.

Results: Within 3-6 months, complete response was achieved in 11 patients (36.6%) and partial response in 4 (13.3%). After longer term therapy, 9 patients (30%) remain with a complete response after a mean of 37 months (range from 12-60 months) with a mean dose of 2.1 mg/wk of cabergoline. Two patients escaped after 2 and 5 years of complete response, but one transiently renormalized UFC after an increase in cabergoline dosage. No long-term response was maintained in 4 initial partial responders.

Conclusions: Cabergoline monotherapy can provide an effective long-term medical therapy for selected patients with CD, but requires close follow-up for dose adjustments.

Abstract

Paediatric Cushing’s disease (CD) is usually associated with growth retardation, but there are only few published data on skeletal maturation at diagnosis. We analysed factors contributing to skeletal maturation and final height in Asian Indian patients with paediatric CD. We conducted retrospective analysis of 48 patients (29 males; 19 females) with mean age: 14.84 years at diagnosis (range 9–19 years). A single observer using the Greulich Pyle method determined the bone age (BA) of each child. BA delay, i.e. the difference between chronological age (CA) and BA, was compared with clinical and biochemical variables. BA delay was present in 35/48 (73%) patients (mean delay 1.6 years, range 0.5–5 years) and correlated negatively with height SDS (r = −0.594, P < 0.001) and positively with CA at diagnosis (r = 0.247, P < 0.05). There was no correlation with duration of symptoms before diagnosis, basal cortisol, midnight cortisol, ACTH or percentage suppression of low dose dexamethasone suppression cortisol (LDDST). We could not demonstrate any relationship between the duration of history before diagnosis and height SDS at final height. Mean final height SDS in patients was −1.84. We found that most children with CD had delayed BA and correlated significantly with CA and height SDS at diagnosis. Early diagnosis may reduce delay in skeletal maturation and thus contribute to optimal catch-up growth.

Sunday, August 8, 2010

SINCE Cushing1 called attention to the syndrome that now bears his name, it has been recognized that the clinical manifestations of Cushing's disease are associated with adrenocortical hyper-function and the secretion of excessive amounts of cortisol. The adrenal abnormalities may be classified as nontumorous hyperplasia, benign adenoma and adrenal carcinoma.

Although the intensity of the symptoms may vary, the disorder has been characterized by an unfavorable prognosis and a progressively deteriorating course. The life expectancy2 of the untreated patient is reported as three to ten years, with an average duration of five to seven years. Patients with malignant adrenocortical tumors . . .

Source Information

NEW HAVEN, CONNECTICUT

† Postdoctoral fellow, Department of Medicine, Yale University School of Medicine.

Objective: To elucidate the long-term outcomes of pituitary adenomas diagnosed in childhood and adolescence, knowledge of which remains sparse.

Design and methods: A neuroendocrine service in Liverpool, United Kingdom. Retrospective review of patients aged less than 21 years at diagnosis of pituitary adenoma during the period 1984-2009.

Results: There were 41 patients (33 female), mean age at diagnosis 17.3 years (range 11 - 21) and mean follow-up 9.6 years; 29 patients had prolactinomas (15 macroprolactinomas), six non-functioning adenomas (NFPA), five Cushing's disease (CD) and one acromegaly. All prolactinomas received dopamine agonists (DAs) and 3 also pituitary surgery. Ten further patients underwent surgery: all five CD, one acromegaly and four NFPA. Four received radiotherapy after surgery. Ten patients receive hormone replacement: nine hydrocortisone, five thyroxine, seven sex steroids and five growth hormone (GH); another 7 have severe asymptomatic GH deficiency. Three female patients were treated for infertility (two successfully). Thirteen patients gained significant weight (body mass index (BMI) increase >2 kg/m2) since diagnosis and 16 in total are now obese (BMI >30 kg/m2). Five are treated with orlistat and one attends a weight management service. Two receive antihypertensive medications, two have type 2 diabetes and four have treated dyslipidaemia.

Conclusions: This is one of the largest reviews of patients aged 21 or younger at diagnosis of pituitary adenoma followed up by a single service. Two-thirds have prolactinomas, all treated with DAs and three underwent surgery. Increased cardiovascular risk factors (obesity and dyslipidaemia) and infertility are important sequelae and active identification and treatment necessary.

This is a case of a 32-year-old woman who presented to the clinic at 11 weeks of gestation after she was found to have an adrenal mass during the work up of hypertension. An MRI prior to pregnancy revealed a right-sided 4.8-cm adrenal mass.

On examination, the patient was overweight, with no other features of Cushing syndrome like striae, buffalo hump, etc. At 15 weeks, her 24-hour urine cortisol was 1095 mcg/24 hours (4.0–50.0 mcg/24 h). Her repeat 24-hour urine cortisol at 21 and 25 weeks of gestation were 1655 and 3039 mcg, respectively. Her morning adrenocorticotropic hormone level was undetectable.

During the second trimester, she developed acne, striae, truncal obesity, and a “buffalo hump.” After consulting with her surgeon, she opted for adrenalectomy after pregnancy. At 22 weeks, she was started on metyrapone 250 mg daily but the urinary free cortisol remain elevated.

She had an emergent C-section at 34 weeks due to fetal heart decelerations. Metyrapone was discontinued after delivery. Surprisingly, the 24-hour urine Cortisol spontaneously dropped to 7.2 mcg prior to surgery.

A repeat CT prior to adrenalectomy revealed an increase in the size of the adrenal mass. The patient had an uneventful laparoscopic right adrenalectomy 2 months after delivery. The pathology was consistent with a cortical adenoma. The largest diameter of the tumor was 9 cm. The patient and the baby remained asymptomatic after the surgery.

Abstract

Introduction. Iatrogenic Cushing's syndrome (CS) is caused by exposure to glucocorticoids and may be promoted by interaction with additional drugs. It is well known in asthmatic human immunodeficiency virus (HIV)-infected patients treated with inhaled fluticasone with ritonavir-containing antiretroviral regimen (cART).

Discussion. Corticosteroids are metabolized by cytochrome P450 3A4 (CYP3A4). Fluticasone has the longest glucocorticoid receptor-binding half-life and is 300 times more lipophilic than budesonide. Inhaled fluticasone possesses a high suppression rate of hypothalamic-pituitary-adrenal axis. Ritonavir, a potent CYP3A4 inhibitor, may inhibit corticosteroid degradation and increase its accumulation. Inhaled budesonide is less likely to cause adrenal suppression.

Diagnosing Cushing's syndrome presents a clinical challenge due to similarities with clinical manifestations and side effects related to cART.

In patients treated with inhaled or intranasal corticosteroids together with cART there may be a higher incidence of iatrogenic CS. CS should be looked for, and management considered carefully.

Having persistent pain, fever or bleeding are usually wake-up calls that something's medically wrong and we should see a doctor. But we sometimes write off subtle or unsightly signs as mere annoyances or cosmetic concerns that we can cover up or ignore. Here are five body signs that women shouldn't overlook:

1. Too Much Facial or Body Hair Hair sprouting in undesirable places, especially on the face and chest (hirsutism), often signals a hormonal imbalance from such conditions as Cushing's syndrome and polycystic ovarian syndrome (PCOS). In fact, PCOS affects 6 to 8 percent of women of childbearing age, and is a major cause of infertility. Other signs of PCOS include acne and being overweight.

Cushing's is a much rarer condition that usually strikes women (and sometimes men) between the ages of 20 and 50. Weight gain, fat on the upper back (aka buffalo hump) with thin arms and legs, round face, irregular periods and fatigue are other common signs. Depending on the cause, various treatments can help correct the hormonal imbalances for both PCOS and Cushing's. Having some facial hair is also fairly common during menopause, when estrogen decreases and androgen increases. However, a lot of facial or body hair in postmenopausal women can signal ovarian cysts or even ovarian cancer.

2. Feeling Cold All the TimeIf you often are cold when others aren't, you may be suffering from an under-active thyroid (hypothyroidism), one of the most under-diagnosed conditions in women. Indeed, more than half of the cases of go undiagnosed. This is very unfortunate since an under-active thyroid causes a plethora of unpleasant signs including weight gain, bags under the eyes or droopy eyelids, constipation, and dry hair, skin and nails. Hypothyroidism is much more common in women than men and usually affects those over the age of 50. It can be treated hormonally.

3. Dry Eyes, Mouth and Skin In winter, many women notice that their eyes and skin are dry and their mouths are parched due to low humidity and over-heated rooms. Mucous membranes can also become dry as a side effect of various medications, as well as from the loss of estrogen that normally accompanies aging. But dry eyes, mouth and other mucous membranes including the vagina, can also signal Sjorgren's syndrome, a potentially serious autoimmune disease that primarily affects women in their 40s and 50s.

Joint inflammation or tenderness is another common sign. Although Sjorgren's is not rare, it often goes undiagnosed or misdiagnosed for years. Unfortunately it's a progressive disease that, without treatment, can cause eye damage, dental decay and gum disease, as well as damage to the digestive and reproductive systems. There is no cure, but early detection and treatment can help alleviate the symptoms and help stop the progression of the disease.

4. Abdominal BloatingOccasional abdominal bloating can be due to a number of digestive conditions such as lactose intolerance and other food sensitivities. However, abdominal bloating or a distended abdomen that lasts more than a few weeks can be an early -− and sometimes the only −- warning sign of ovarian cancer, one of the deadliest cancers in women. Other signs may include difficulty eating or feeling full quickly after eating or having frequent or urgent needs to urinate. About 80 percent of ovarian cancers have spread (metastasized) before they're diagnosed, but if detected and treated early the prognosis can be good.

5. A Discolored, Swollen BreastMany women get swollen breasts before their periods and when they're pregnant. But if you have one swollen breast that's red or discolored and feels warm, it may be a warning sign of inflammatory breast cancer (IBC), a rare but very aggressive form of breast cancer. Unfortunately, IBC is often misdiagnosed by doctors as an infection or even an insect bite. And, unlike with other forms of breast cancer, most women with IBC do not have a breast lump. Their breast may also be dimpled like the skin of an orange, and may be tender, itchy, or achy. With early diagnosis and treatment, more women are now surviving this deadly form of breast cancer.

If you notice any of these or other disturbing signs, be sure to mention them to your doctor as soon as possible. He or she can determine whether it's something you can safely ignore or something that warrants further diagnosis or treatment.

Monday, August 2, 2010

Monday, August 02, 2010 Over 20 million children under the age of five are overweight, indicate latest WHO statistics. Obesity is on the rise and has reached epidemic proportions in the world. About twenty percent of children are either overweight or obese.

The Body Mass Index (BMI) estimates the ideal weight of a person based on his size and weight. It is valid for an adult man or woman (18 to 65 years). Doctors often use it to measure obesity. BMI is equal to a person's weight in kilograms (kg) divided by his height in meters (m) squared. Adults with a BMI of 30 or higher are considered obese. But those having a BMI of 40 or more are extremely obese.

It's a common belief that eating too much and exercising too little is the main cause of gaining weight. But this is not true all the time. It is my personal observation that some people eat a lot but they do not gain weight. They are quite healthy, slim and smart. And there are many who take very little food, but they are overweight. You may also have observed the same.

There is another set of people who eat a lot but keep losing weight. It shows there are other factors involved in obesity rather than the eating habit alone.

Genes play a great role in tendencies to gain weight or lose weight. There may be more chances to develop obesity if one or both parents are obese. Some studies have shown that certain drugs, such as steroids, antidepressants, high blood pressure, medications used to lower blood sugar such as insulin may cause excessive weight gain.

For some people, emotions influence their eating habits. Many people eat excessively in response to boredom, sadness, stress or anger. While most overweight people have no more psychological disturbances than normal weight people, about 30 percent of the people who seek treatment for serious weight problems have difficulties with binge eating. Diseases such as hypothyroidism, insulin resistance, polycystic ovary syndrome and Cushing's syndrome also contribute to obesity.

Women tend to be more overweight than men. Men burn more energy at rest than women, so men require more calories to maintain their body weight. The metabolic rate decreases in women when they reach the postmenopausal age. That is partly why many women gain weight after menopause.

Obesity is not just a cosmetic consideration. It is widely known that obesity is the fertile land for disease. Health problems start when someone starts getting overweight, and the likelihood of problems increases as someone becomes more and more overweight. Many of these conditions cause long-term suffering for individuals and families such as cardiovascular disease, type 2 diabetes, osteoarthritis (degenerative arthritis) of the knees, hips, and the lower back.

A very interesting Norwegian study showed that obesity tended to increase blood pressure more significantly in women than in men. The risk of developing high blood pressure is also higher in obese people who are apple shaped (central obesity) than in people who are pear shaped (fat distribution mainly in hips and thighs).

There are a lot of treatments available in the market for obesity. But almost all of them are associated with serious side effects and toxicity except homeopathy. Homeopathy is a time tested, proven method to cure obesity. The writer has also seen amazing results in treating obesity in the patients who were determined and followed the instructions carefully.

International research shows that homeopathic medicines are extremely effective in reducing weight by improving the metabolic system, digestive system and elementary system.

Homeopathy is the fastest growing system of medicine in the world. There is wider acceptance of homeopathy in such countries as France, Germany, Mexico, Argentina, India and Great Britain. The British royal family is patronizing the Royal London Homoeopathic Hospital for the last one hundred years and prefer taking homeopathic treatment when needed.

It is not necessary to achieve an 'ideal weight' to derive health benefits from obesity treatment. Instead, the goal of treatment should be to reach and hold to a 'healthier weight.' The emphasis of treatment should be to commit to the process of life-long healthy living including eating more wisely and increasing physical activity. In sum, the goal in dealing with obesity is to achieve and maintain a 'healthier weight.'

On the popular reality TV show, "Dr. G: Medical Examiner," Arden Monroe-Obermeit battled a rare disease while working as a morgue technician.

This weekend, she'll graduate with a nursing degree from the University of Central Florida. She's eager to help others stay healthy so they don't become the medical examiner's next case.

Monroe-Obermeit's eight years of performing more than 3,000 autopsies and 500 death scene investigations, as well as a life-changing experience with a nurse practitioner, drove her to enroll in UCF's College of Nursing.

"I saw too many deaths caused by people ignoring their diabetes or their heart conditions," said Monroe-Obermeit. "In nursing, I absolutely love teaching patients how to avoid becoming a case at the morgue."

Monroe-Obermeit will be among the 3,032 anticipated graduates this semester. Ceremonies will be held at 9 a.m. and 2 p.m. on Saturday, Aug. 7, at the UCF Arena.

During her four years on the Discovery Channel television show, Monroe-Obermeit battled her own health issues, which she said many doctors were not able to diagnose. She long suspected Cushing's syndrome, a rare disorder that causes high levels of the hormone cortisol and results in a myriad of symptoms, including fatigue and weight gain.

It was a nurse practitioner who finally ordered radiological studies that helped her obtain the Cushing's diagnosis and get treatment. Medical specialists then surgically removed a tumor from her pituitary gland. After treatment, she quickly lost 80 pounds. Her TV fans noticed and applauded her in fan mail and blogs.

"A nurse practitioner made a huge impact on my life by helping me obtain a very difficult and rare diagnosis," she said. "The impact she had on me was inspiring. My dream is to be able to do that for just one of my patients in the future."

Monroe-Obermeit, who already holds a bachelor's degree in Biological Anthropology from the University of Florida, will enter the new post-baccalaureate Doctor of Nursing Practice program in the fall to prepare for certification as a family nurse practitioner.

Commencement Details

The anticipated summer graduates include 2,386 students who filed for bachelor's degrees, 515 for master's degrees, two for education specialist degrees and 129 for doctoral degrees.

UCF President John Hitt will award the 150,000th degree of his 18-year career at the summer ceremonies. Of the more than 203,000 degrees that UCF will have awarded after the two ceremonies, President Hitt will have awarded more than 151,600.

The 2 p.m. ceremony will feature the inaugural graduating class of UCF's post-master’s Doctor of Nursing Practice program. The post-master's program teaches advanced practice nurses to perform at the highest level and prepares them for leadership roles in patient care.

The 9 a.m. ceremony will feature graduates of: College of Arts and Humanities, College of Business Administration, College of Education, College of Graduate Studies, Office of Undergraduate Studies and Rosen College of Hospitality Management. State Rep. Larry Cretul, speaker of the Florida House, will be the speaker. His district includes Marion and Levy counties, which UCF serves in partnership with the College of Central Florida.

The 2 p.m. ceremony will include graduates from: College of Engineering and Computer Science, College of Health and Public Affairs, College of Medicine’s Burnett School of Biomedical Sciences, College of Nursing, College of Optics and Photonics and College of Sciences. The speaker will be Ronald Rogers, president of Ronald O. Rogers & Associates management firm in Orlando. He is a noted civic leader who was named Humanitarian of the Year by the Orange County Community Action Agency.

The procession of graduates will begin 20 minutes before the start times of each ceremony.

Guests need tickets to attend the ceremonies. Guests without tickets can watch live broadcasts of all ceremonies at the Fairwinds Alumni Center across from the UCF Arena. Webcasts also are available live and after the ceremonies at http://webcast.oir.ucf.edu.

Of the more than 203,000 degrees that UCF will have awarded after the two ceremonies, President Hitt will have awarded more than 151,600. He awarded the 25,000th master's degree of his 17-year career at UCF in December, and the 200,000th bachelor's degree in May.

UCF Stands For Opportunity: The University of Central Florida is a metropolitan research university that ranks as the 3rd largest in the nation with more than 53,500 students. UCF's first classes were offered in 1968. The university offers impressive academic and research environments that power the region's economic development. UCF's culture of opportunity is driven by our diversity, Orlando environment, history of entrepreneurship and our youth, relevance and energy. For more information visit http://news.ucf.edu.

Received 4 August 2009; received in revised form 16 January 2010; accepted 19 January 2010.

Summary

Glucocorticoid dyshomeostasis is observed in a proportion of depressed individuals. As a result, glucocorticoid receptor (GR) antagonists are currently being tested as potential anti-depressants. The current study was designed to test the efficacy of mifepristone, a GR antagonist, in mitigating behavioral, neuroendocrine and central nervous system (CNS) responses to an acute stressor. Adult male rats were treated for 5 days with mifepristone (10mg/kg) and then exposed to the forced swim test (FST). Treatment with mifepristone decreased immobility and increased swimming (but not climbing) behavior in the FST, consistent with anti-depressant action. In addition, mifepristone dampened the ACTH response to FST exposure. In the CNS, mifepristone increased c-Fos expression in all subdivisions of the medial prefrontal cortex (mPFC) and decreased neuronal activity in some subdivisions of the hippocampus including the CA2, CA3, and hilus region of the dentate gyrus in animals exposed to FST. In contrast, mifepristone increased neuronal activity in the ventral subiculum (output region of the hippocampus) and decreased c-Fos expression in the central amygdala (CeA) in animals exposed to FST. These data suggest that anti-depressant efficacy and perhaps HPA dampening properties of RU486 are related to alterations in key limbic circuits mediating CNS stress responses, resulting in enhanced stress inhibition (via the mPFC and ventral subiculum) as well as decreased stress excitation (central amygdala). Overall the data suggest that drugs targeting the glucocorticoid receptor may ameliorate stress dysfunction associated with depressive illness.

About Me

I am a Cushing's patient who has dealt with Cushing's symptoms since 1983 (or earlier) and the aftereffects of pituitary surgery since 1987.

Because I had very little support for my symptoms, diagnosis and surgery, I decided to try to make things a little better for other patients and started a support site called Cushing's Help and Support in 2000. The site has grown to astronomical numbers. This disease isn't as rare as doctors have told us!

In 2006, I was also diagnosed with kidney cancer (renal cell carcinoma). My left kidney and adrenal gland were removed. Having an adrenal gland removed complicates my post-Cushing's symptoms.